Although adolescents entering treatment for substance abuse typically use several substances, alcohol is seldom the drug of choice. Given alcohol's role as a gateway substance in the initiation of substance misuse, the authors hypothesize that alcohol is substantially involved in adolescent relapse following substance abuse treatment. One hundred fifty-seven youths (39.5% female, mean age 15.91 years) were recruited from adolescent inpatient alcohol and drug treatment centers and assessed at six and 12 months after discharge. Of the youths studied, 79% had used one or more substances by 12-month follow-up. Although only 1% reported alcohol as their substance of choice while hospitalized, alcohol was involved in 46% of initial posttreatment use episodes. Almost a quarter (23%) of initial posttreatment substance use events involved multiple substances. Initial posttreatment use episodes involving multiple substances and preferred substances were associated with poorer outcomes during the year following treatment both in terms of rate of return to and severity of substance involvement. Youths who initially used only alcohol were also likely to resume harmful levels of substance involvement by one year after treatment. Results suggest two routes, gateway and preferred substance, for adolescents in the resumption of harmful substance use following treatment. This gateway role merits consideration by adolescent substance abuse treatment providers and families of treated youths.